Table 2. Adverse Events Occurring Up to 5 Days After Oral Challenge.
| Variable | Adverse events, No. (%) | |
|---|---|---|
| Intervention group (n = 22) | Control group (n = 24) | |
| Type of adverse event | ||
| An antibiotic-associated adverse event (any nonimmune mediated reaction) | 6 (27) | 2 (8) |
| Nausea/vomiting/diarrhea | 2 (9) | 0 |
| Immediate diffuse rash/urticaria | 2 (9) | 1 (4) |
| Delayed diffuse rash/urticaria (>1 h) | 6 (27) | 3 (12) |
| Other nonsevere adverse events | 6 (27) | 18 (75) |
| Angioedema/laryngeal involvement/respiratory compromise | 0 | 0 |
| Anaphylaxis (or unexplained collapse) | 0 | 0 |
| Death | 0 | 0 |
| Timing | ||
| <1 h | 6 (27) | 5 (21) |
| 1-12 h | 9 (41) | 9 (38) |
| 13-24 h | 3 (14) | 2 (8) |
| 25-48 h | 2 (9) | 4 (17) |
| 2-5 d | 2 (9) | 4 (17) |
| Time since oral challenge, median (IQR), h | 4.1 (0.7-16.7) | 6.9 (2.1-35.1) |
| Severitya | ||
| Grade 1 | 17 (77) | 16 (67) |
| Grade 2 | 5 (23) | 8 (33) |
| Degree of causalityb | ||
| Certain | 2 (9) | 1 (4) |
| Probable/likely | 6 (27) | 4 (17) |
| Possible | 7 (32) | 5 (21) |
| Unlikely | 6 (27) | 14 (58) |
| Unassessable/unclassifiable | 1 (5) | 0 |
| Management | ||
| None | 13 (59) | 16 (67) |
| Rechallenge | 0 | 1 (4) |
| Withdrew from study | 0 | 0 |
| Otherc | 0 | 2 (8) |
| Drug therapy | ||
| Oral antihistamine | 9 (41) | 6 (25) |
| Otherd | 2 (9) | 5 (21) |
| Emergency department referral | 0 | 0 |
| Intensive care unit referral | 0 | 0 |
| Calculated duration of adverse event, median (IQR), h | 11 (1.2-48.3) | 60 (2-76) |
| Recovered/resolved | 22 (100) | 20 (83)e |
Grade 1: asymptomatic or mild symptoms from clinical or diagnostic observations only with no intervention indicated; grade 2: moderate symptoms limiting age-appropriate instrumental activities of daily living with minimal, local, or noninvasive intervention indicated.
Certain: an event with plausible time relationship to drug intake that cannot be explained by disease or other drugs and is definitive pharmacologically or phenomenologically (ie, an objective and specific medical disorder or a recognized pharmacological phenomenon); probable/likely: an event with reasonable time relationship to drug intake that is unlikely to be attributed to disease or other drugs and response to withdrawal is clinically reasonable; possible: an event with reasonable time relationship to drug intake that could also be explained by disease or other drugs and information on drug withdrawal may be lacking or unclear; unlikely: an event with a time to drug intake that makes a relationship improbable (but not impossible) and disease or other drugs provide plausible explanations; and unassessable/unclassifiable: a report suggesting an adverse reaction that cannot be judged because the information is insufficient or contradictory and data cannot be supplemented or verified.
Other management included the use of an intranasal corticosteroid spray (n = 1) and scheduled return to clinic for repeat skin testing and delayed intradermal reads and prolonged oral challenges (n = 1).
Other administered treatments included (1) a combination of acetylsalicylic acid, butalbital, and caffeine for headache, and (2) loperamide in the intervention group, as well as (1) intranasal corticosteroid spray, (2) intravaginal clotrimazole cream, and (3) oral paracetamol/acetaminophen for 3 patients in the control group.
Details regarding the outcomes of the adverse events in the control group: (1) 1 patient presented with a headache and was under treatment with acetaminophen during the assessment; (2) 1 patient presented with Candida vulvovaginitis and received intravaginal clotrimazole for 7 days, though despite resolution of her initial symptoms she had recurrent symptoms 3 weeks later, and it was considered that she recovered with sequelae; (3) 1 patient reported nasal irritation and also noticed recurrent symptoms following the patient’s chemotherapy cycle, and it was considered that the reported symptoms were related to the chemotherapy and not the penicillin challenge; and (4) 1 patient developed a single blister (<1 cm) on the chest that had decreased but was still present at the 5-day assessment. The rest of the patients in control arm (n = 20 [83%]) and all of the patients in the intervention arm (n = 22 [100%]) recovered from their adverse event.